Human apyrase represents a highly promising therapy for acute ischemic stroke which is a leading cause of death and disability with almost no effective therapy for most patients. This enzyme strongly inhibits platelet activation and aggregation with modest bleeding risk. We will validate hypothesis that in thromboembolic model of stroke in rats, combination treatment of ASA plus apyrase at acute stage provides more effective protection than ASA or apyrase alone in short term as well as long-term experiments without increasing intracerebral hemorrhage. PUBLIC HEALTH RELEVANCE: We will utilize clinically relevant embolic stroke models in rats to assess neuroprotective effect of aspirin and apyrase treatment.